Title |
Neutralization mechanism of a highly potent antibody against Zika virus
|
---|---|
Published in |
Nature Communications, November 2016
|
DOI | 10.1038/ncomms13679 |
Pubmed ID | |
Authors |
Shuijun Zhang, Victor A. Kostyuchenko, Thiam-Seng Ng, Xin-Ni Lim, Justin S. G. Ooi, Sebastian Lambert, Ter Yong Tan, Douglas G. Widman, Jian Shi, Ralph S. Baric, Shee-Mei Lok |
Abstract |
The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies for ZIKV cross-neutralization activity showed antibody C10 as one of the most potent. To investigate the ability of the antibody to block fusion, we determined the cryoEM structures of the C10-ZIKV complex at pH levels mimicking the extracellular (pH8.0), early (pH6.5) and late endosomal (pH5.0) environments. The 4.0 Å resolution pH8.0 complex structure shows that the antibody binds to E proteins residues at the intra-dimer interface, and the virus quaternary structure-dependent inter-dimer and inter-raft interfaces. At pH6.5, antibody C10 locks all virus surface E proteins, and at pH5.0, it locks the E protein raft structure, suggesting that it prevents the structural rearrangement of the E proteins during the fusion event-a vital step for infection. This suggests antibody C10 could be a good therapeutic candidate. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 8 | 29% |
France | 2 | 7% |
Spain | 2 | 7% |
Netherlands | 2 | 7% |
Ecuador | 1 | 4% |
Hungary | 1 | 4% |
Mexico | 1 | 4% |
Italy | 1 | 4% |
Unknown | 10 | 36% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 18 | 64% |
Scientists | 9 | 32% |
Practitioners (doctors, other healthcare professionals) | 1 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 167 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 32 | 19% |
Researcher | 30 | 18% |
Student > Master | 26 | 16% |
Student > Bachelor | 25 | 15% |
Professor > Associate Professor | 6 | 4% |
Other | 18 | 11% |
Unknown | 30 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 42 | 25% |
Immunology and Microbiology | 27 | 16% |
Agricultural and Biological Sciences | 22 | 13% |
Medicine and Dentistry | 11 | 7% |
Chemistry | 8 | 5% |
Other | 23 | 14% |
Unknown | 34 | 20% |